Condition category
Signs and Symptoms
Date applied
26/02/2007
Date assigned
26/02/2007
Last edited
15/10/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof J J van Hilten

ORCID ID

Contact details

Leiden University Medical Centre (LUMC)
Department of Neurology
Postzone K-05Q
P.O. Box 9600
Albinusdreef 2
Leiden
2300 RC
Netherlands
+31 (0)71 526 6065
J.J.van_Hilten@lumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

P01.098; NTR403

Study information

Scientific title

Acronym

The BIRD study

Study hypothesis

Dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen (ITB).

Ethics approval

Approval received from the local ethics committee (Commissie Medische Ethiek) on the 2nd November 2001 (ref: P01.098).

Study design

Part one: a single blinded placebo-run-in, dose-escalation design
Part two: thereafter, in responders, an open trial

Primary study design

Interventional

Secondary study design

Single-centre

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Reflex sympathetic dystrophy (RSD)

Intervention

Screening phase:
To evaluate the efficacy of ITB a percutaneous catheter is introduced into the lumbar subarachnoid space. All patients will start with a two-day placebo run-in, followed by a gradual titration of continuous intrathecal baclofen through an external pump. The daily baclofen dose will be increased according to a fixed schedule (200, 250, 300, 375, 450, 500, 600, 700 and 800 µg/24 hours).

Depending on the response, the duration of the screening procedure may vary from one to two weeks. If a baclofen-related side-effect occurs at a particular dose, then depending on the severity of the side-effect the pump will be stopped or adjusted to a lower infusion rate.
The outcome that is evaluated to determine if a patient will be implanted is the difference in change between Global Dystonia Severity (GDS - Visual Analogue Scale on which symptom severity is rated from zero [absent] to ten [most severe]) on ITB and placebo days.

This difference is calculated through the following steps:
1. GDSbaclo: for each ITB day the sumscore of six one-hour intervals (11.00 a.m. - 4.00 p.m.) is determined. Likewise, for the two placebo days a mean placebo-sumscore is calculated (GDSplacebo)
2. GDShome: a similar mean sumscore of six one-hour intervals of the GDS at home is determined
3. For each day the GDS change score is calculated as follows:

GDSbaclo - GDShome = GDSchangescore1, expressed in % (calculated for each ITB day)

GDSplacebo - GDShome = GDSchangescore2, expressed in % (calculated for the mean of the two placebo days)

Criteria for being a candidate for pump implantation: a greater than or equal to 25% difference between the GDSchangescore1 and GDSchangescore2 present on two subsequent days (responder).

Implantation phase:
After the screening phase a programmable pump (SynchroMed Infusion system, Medtronic INC, Minneapolis MN) for continuous ITB administration will be implanted in patients who fulfill the criteria stated above. During this phase ITB therapy will be started at a dose double the effective screening dose and will be titrated for a maximum effect over a three-month period. All implanted patients will be co-managed by the department of rehabilitation. Following implantation, severely affected patient will be referred to an in-patient rehabilitation unit. Mild to moderately affected patients will be seen in the out-patient rehabilitation unit.

Intervention type

Drug

Phase

Not Specified

Drug names

Intrathecal baclofen (ITB)

Primary outcome measures

1. GDS will be calculated separately at baseline (GDShome) and during a week at one year of follow-up. The difference between these two measurements is identified as the change from baseline in GDS at one-year follow-up (GDS1year)
2. Dystonia related Functional Limitations (DFL) are self-assessed at hourly intervals across the day using four items, addressing upper extremity function, capability of making transfers and mobility. Each item is assessed on a zero to three scale. DFL will be calculated at baseline (DFLhome) and during a week at one year of follow-up.

The difference between these two measurements is identified as the change from baseline in DFL at one year follow-up (DFL1year).

Secondary outcome measures

1. RSD related impairments
2. Activities of Daily Living (ADL) and quality of life will be assessed separately before implantation and at one-year follow-up

The difference between these two measurements is identified as the change from baseline for each score.

Overall trial start date

01/01/2002

Overall trial end date

01/01/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. All patients should fulfill the diagnostic criteria of the complex regional pain syndrome consensus report of the International Association for the Study of Pain (IASP):
1.1. Continuing pain, allodynia or hyperalgesia, in which the pain is disproportionate to any inciting event
1.2. Evidence at some time of oedema, changes in skin blood flow, or abnormal sudomotor activity in the region of the pain
1.3. No condition that would otherwise account for the degree of pain and dysfunction
2. All patients must suffer from tonic dystonia in one or more extremities, that may cause fixed postures at rest of variable severity
3. Before starting the study all patients will have received a trial with oral baclofen. Only patients with an insufficient response or dose-limiting sedative effects to oral baclofen are eligible for this study

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

45

Participant exclusion criteria

Does not comply with the above inclusion criteria

Recruitment start date

01/01/2002

Recruitment end date

01/01/2006

Locations

Countries of recruitment

Netherlands

Trial participating centre

Leiden University Medical Centre (LUMC)
Leiden
2300 RC
Netherlands

Sponsor information

Organisation

Leiden University Medical Centre (LUMC) (The Netherlands)

Sponsor details

Department of Neurology
P.O. Box 9600
Leiden
2300 RC
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.lumc.nl/english/start_english.html

Funders

Funder type

Industry

Funder name

Leiden University Medical Centre (LUMC) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medtronic Europe S.A. (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes